Fats result from the accumulation of redundant energies of ingested foods in white adipose tissues. Excessively accumulated white adipose tissues lead to obesity, which consequently causes not only various lifestyle-related diseases but great aesthetic problems. Recently, scientific evidence has demonstrated that, particularly, increase in perivisceral (mesenteric) white adipose tissues triggers hypertension, insulin resistance, abnormal glucose tolerance or hyperlipemia and thereby causes metabolic syndrome. Thus, prevention and improvement thereof have been socially desired.
The hypertrophy of adipose cells attributed to the accumulated fats decreases the secretion of good adipokines from the adipose cells and in turn causes the secretion of various bad adipokines (e.g., TNFα and resistin), resulting in insulin resistance (i.e., reduced insulin sensitivity). As a result, the blood glucose level is insufficiently reduced. Thus, insulin is excessively secreted for controlling the blood glucose level, causing hyperinsulinemia. Upon onset of hyperinsulinemia, the effect of excessive insulin on lipid metabolism, for example, causes metabolic syndrome.
Adiponectin, a good adipokine, promotes the combustion of fatty acids and sugar uptake and improves insulin resistance (non-patent document 1). The combustion effect of adiponectin on fatty acids is not produced by adipose cells, but is attributed to the activation of AMP-activated protein kinase (AMPK) in the liver and skeletal muscles. Adiponectin inhibits gluconeogenesis and stimulates the combustion of fatty acids in the liver, while it stimulates sugar uptake and the combustion of fatty acids in the skeletal muscles.
The expression of adiponectin is induced along with the differentiation of adipose precursor cells into adipose cells. Adiponectin is actively secreted from non-hypertrophied adipose cells. By contrast, adiponectin from hypertrophied adipose cells has an attenuated effect due to the TNFα or the like. In addition, the transcription of adiponectin is inhibited in the hypertrophied adipose cells, and the resulting deficiency of adiponectin causes metabolic abnormality (non-patent document 1).
Vegetable- or fruit-derived carotenoid has been reported to inhibit the differentiation of adipose precursor cells into adipose cells during insulin induction (patent document 1). If the differentiation of adipose precursor cells into adipose cells is inhibited, the expression of adiponectin is also inhibited, as described above. Thus, it is doubtful whether the inhibited differentiation into adipose cells directly leads to an antiobesity effect.
Various studies have previously been conducted on the prevention and improvement of obesity by means of limitations on ingested energies, such as dietary restriction, the delay and inhibition of absorption of excessive energies, or search for carbohydrate absorption inhibitors working in gastrointestinal tracts. The limitations on energy ingestion, however, also serve as factors reducing a basal metabolic rate and do not always improve obesity. Thus, ideally, the accumulated fats are aggressively metabolized and digested and then given off as thermal energies to decrease obesity. From these viewpoints, food materials have been actively searched for functional ingredients having a lipolysis-promoting effect in recent years, and many lipolysis promoters and foods or drinks have been proposed.
Known active ingredients in naturally occurring lipolysis promoters include plants of the family Rutaceae (patent document 2), plants of the genus Cirsium (patent document 3), plants of the family Piperaceae (patent document 4), orange leaves, orange flowers, coltsfoot leaves, and calamus roots (patent document 5), and pearl-barley, barley, cassia seeds, guava, and pu-erh tea (patent document 6). Furthermore, examples of lipolysis promoters that have been found recently can include a lipolysis promoter comprising Nelumbo nucifera or an extract thereof as an active ingredient (patent document 7), a lipolysis promoter containing at least any of an extract of white birch of the family Betulaceae and an extract of kumazasa of the family Poaceae (patent document 8), and a fat accumulation inhibitor and a promoter containing a hydrolysate of a wheat protein (patent document 9).
Meanwhile, hypertension is a typical symptom of metabolic syndrome and has affected an increasing number of patients year after year. Hypertension is known to cause various complications such as cerebral hemorrhage, subarachnoid hemorrhage, cerebral infarction, myocardial infarction, angina pectoris, and nephrosclerosis. Various studies have been conducted on the pathogenic mechanism of hypertension, and the renin-angiotensin system involved in rise in blood pressure and the kallikrein-kinin system involved in decrease in blood pressure are known to play an important role therein. In the renin-angiotensin system, angiotensinogen secreted from the liver is principally converted to angiotensin I by renin produced in the kidney and further converted to angiotensin II by an angiotensin-converting enzyme (ACE). This angiotensin II contracts vascular smooth muscles and raises blood pressure. On the other hand, kallikrein in the hypotensive system acts on kininogen to produce bradykinin. This bradykinin has the effect of decreasing blood pressure by vasodilation, whereas ACE acts to digest this bradykinin. It has thus been revealed that ACE is involved in a rise in blood pressure by two effects: the production of the hypertensive peptide angiotensin II and the inactivation of the hypotensive peptide bradykinin. Thus, the inhibition of the enzymatic activity of this ACE enables a rise in blood pressure to be prevented. For example, captopril or enalapril, which is a proline derivative developed as a substance having an ACE inhibitory activity, is widely used in the treatment of hypertension.
Also, peptides obtained by enzymatically digesting food material proteins have recently been reported to have an ACE inhibitory activity. There are many reports on, for example, a collagenase digest of gelatin (patent document 10), a tryptic digest of casein (patent documents to 16), a thermolysin digest of γ-casein (patent document 17), a peptic digest of a sardine muscle (patent document 18), a thermolysin digest of dried-bonito shavings (patent document 19), a thermolysin digest of a sesame protein (patent document 20), and peptic and other digests of κ-casein (patent document 21).